Analysis of clinical phenotypes and genetic variants in two children with sporadic cleidocranial dysplasia / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotypes and genetic diagnosis of 2 sporadic cases for cleidocranial dysplasia.@*METHODS@#The clinical data of two cases of CCD admitted to the Third Affiliated Hospital of Zhengzhou University on December 16, 2021 and December 9, 2021 were analyzed retrospectively, and the whole exome sequencing (WES), chromosome microarray analysis and copy number variation sequencing were performed.@*RESULTS@#The main ultrasonographic findings of the fetus had included poorly calcified skull bones, budging of parieto-occipital area, compression and deformation of skull, and loss of nasal bone. The infant's clinical phenotypes included delayed closure of anterior fontanelle, recurrent respiratory tract infection, growth retardation, and clavicular hypoplasia. By WES analysis, the fetus was found to harbor a heterozygous c.911_914delinsTTT variant of the RUNX2 gene, whilst the infant was found to harbor a heterozygous c.1008delT variant of the RUNX2 gene. Both variants were verified by Sanger sequencing to have occurred de novo.@*CONCLUSION@#For sporadic cases featuring cleidocranial dysplasia, prenatal ultrasonography is particularly important. Hypoplastic clavicle, skull calcification and nasal bone absence are the main features. Diagnosis should also be suspected for infants featuring growth retardation, recurrent respiratory tract infections and clavicular dysplasia. The identification of the c.911_914delinsTTT and c.1008delT variants of the RUNX2 gene has facilitated genetic counseling and prenatal diagnosis, and also expanded the mutational spectrum of the RUNX2 gene.

Clinical phenotype and genetic analysis of a fetus with Glutaracidemia type II C / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type II C (GA II C).@*METHODS@#Clinical data of a 32-year-old pregnant woman and her fetus with GA II C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq).@*RESULTS@#At 18 weeks' gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks' gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c.1285+1G＞A and c.343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PS3_Supporting; PVS1+PM2_Supporting+PM3).@*CONCLUSION@#The c.1285+1G＞A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus. Type II C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.

Diagnosis of a Primary Pleomorphic Liposarcoma in a Tree Shrew（Tupaia belangeri subsp. yaoshanensis） / 实验动物与比较医学

A large spontaneous mass on the dorsal abdomen near the hip joint was found in an aged female Tupaia belangeri subsp. yaoshanensis after 5 years of routine feeding. The tumor in the diseased tree shrew was huge, with an intact surface and no ulceration; however, it caused inconvenience in movement while maintaining a good mental state. After inhalation anesthesia with isoflurane (2%-4%), the tree shrew was euthanized after the tree shrew entered deep anesthesia. Anatomical dissection of the tumor, the tumor boundary was unclear and infiltrated into surrounding tissues. HE staining showed that small focal pleomorphism and large areas of adipocytes were seen in the tumor tissue. The pleomorphic sarcoma area was mainly composed of atypical epithelioid cells with easily visible nuclear divisions. The size of the adipocytes was significantly different, and more pleomorphic adipocytes were seen. The cell volume was large, the nucleus was deeply stained and deformed, the edge was impressed, and the cytoplasm was seen with multiple vesicular lipid droplets. Immunohistochemical results showed that the tumor cells were positive for Vimentin, the small focal polymorphic adipocyte nucleus was positive for S-100, and Ki-67 exhibited a higher proportion of positivity. Combined with HE staining and immunohistochemical results, the spontaneous tumor in this tree shrew was comprehensively diagnosed as pleomorphic liposarcoma.

Diagnosis of Trichoepithelioma in a Tree Shrew and Observation of Cell Biological Characteristics / 实验动物与比较医学

ObjectiveTo observe the primary tumor of tree shrews and to provide a basis for studying the pathogenesis and prevention of trichoepithelioma. MethodsA tumor was discovered in the chest and abdomen of a tree shrew during natural cultivation. The tree shrew was anesthetized, and the tumor was surgically removed. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed on the tumor tissue after paraffin section, and the tumor cells were isolated and cultured by passage. The isolated tumor cells were subcutaneously injected into healthy tree shrews and nude mice. The tumorigenesis of tumor cells in vivo was observed once a day, with nude mice continuously observed for 2 months and tree shrews observed for more than 6 months. ResultsHE staining showed that the basal cells in the dermis were arranged as a whole, like a string of petals, forming nests and stripe-like structures with clear boundaries. The observation results after magnification revealed that the tumor cells were arranged in a pallisade-like and basal pattern, with deep nuclear staining and minimal cytoplasmic. Immunohistochemical staining showed the high expression of CK protein and low proportion expression of ki-67 protein in tumor cells, as well as the high expression of vimentin and low expressions of Bcl2 and CD10 in tumor cell mesenchyme. The isolated tumor cells grew well in DMEM medium containing 10% fetal bovine serum and could be cultured by passage, but no tumor formation was observed in healthy tree shrews and nude mice inoculated with tumor cells. ConclusionCombined with the location of the tumor, overall morphology, HE staining, and immunohistochemical results, the thoracoabdominal mass of the tree shrew was diagnosed as a trichoepithelioma.

Application and analysis of competition based training mode for first aid skills in residency program / 中华急诊医学杂志

Objective:To explore the model of first aid skills training based on competition.Method:The second-year residents who participated in the competition in 2021 ( n = 142) were selected. According to whether they attended BLS training in the first year, they were divided into group A ( n = 88) who attended BLS training and group B ( n = 54) who did not. Chi-square test, T test, Wilcoxon rank sum test and Logistic regression were used in our study. Results:There was no significant difference in gender and specialty between both groups (female, 62.5% vs. 68.5%, P= 0.466; TCM, 50% vs. 53.7%, P= 0.668), but the real resuscitation experience of group A was more than that of group B (40.9% vs. 9.3%, P= 0.000). The qualified rate of CPR and the compression score in group A was higher than that in group B [(81.8% vs. 61.1%, P = 0.006; (30±5) vs. (25 ±10), P= 0.001], including compression frequency, depth, rebound and compression/respiration rate (73.9% vs. 55.6%, P= 0.024; 88.6% vs. 70.4%, P= 0.006; 96.6% vs. 87%, P= 0.031). In the theoretical examination, the correct rates of electrocardiogram [(53.63±2.9)% vs. (50.44±2.57)%] and first aid medication [(57.38±3.55)%, P = 0.001] in the two groups were significantly lower than the qualified rate. After adjusting other factors, Logistic regression analysis showed that the CPR qualification rate in group A was 2.769 times higher than that in group B ( P= 0.015, 95% CI 1.215~6.311) Conclusions:The first aid skills training mode based on competition can objectively reflect first aid skills level of residents. We found that the quality of CPR skills was not related to gender, specialty and real CPR experiences but experience of BLS training was an independent influencing factor. And how to identify and manage arrhythmias and how to choose different emergency drugs are urgent emergency skills for residents to improve.

Evaluation the application of intra-operative cell salvage in cesarean section based on multicenter data / 中华妇产科杂志

Objective:To investigate the safety, efficacy and application indication of intra-operative cell salvage (IOCS) in cesarean section.Methods:A total of 1 265 pregnant women who received IOCS blood transfusion during cesarean section in 11 tertiary A hospitals from August 2016 to January 2019 were collected and divided into <1 500 ml group (796 cases) and ≥1 500 ml group (469 cases) according to the amount of blood loss during cesarean section. The general clinical data, ultrasonic imaging data, perinatal and puerperium indicators were analyzed retrospectively. The risk factors of intraoperative blood loss ≥1 500 mL using IOCS transfusion were analyzed by logistic multivariate regression.Results:(1) A total of 848 001 ml of blood was recovered and a total of 418 649 ml of blood was transfused in 1 265 pregnant women who received IOCS transfusions, which was equivalent to 23 258 U red blood cell suspension, greatly saving medical resources. The intraoperative blood loss in <1 500 ml group and ≥1 500 ml group was 800 ml (300-1 453 ml) and 2 335 ml (1 500-20 000 ml), respectively. No amniotic fluid embolism, severe adverse reactions, shock and death occurred in the two groups. (3) Multivariate regression analysis showed that age ≥35 years ( OR=1.5, 95% CI: 1.1-1.9), prenatal hemoglobin level <110 g/L ( OR=1.7, 95% CI: 1.3-2.2), history of uterine surgery ( OR=1.8, 95% CI: 1.3-2.6), placenta previa ( OR=1.9, 95% CI: 1.1-3.1), placenta accreta ( OR=2.6, 95% CI: 1.8-3.9), blood pool in the placenta ( OR=1.6, 95% CI: 1.1-2.3), abnormal posterior placenta muscle wall ( OR=1.8, 95% CI: 1.2-2.6), placenta projecting to the anterior uterine wall ( OR=3.0, 95% CI: 1.3-7.0) were risk factors for blood loss ≥1 500 ml in obstetric transfusion using IOCS technique, with statistical significance (all P<0.05). Conclusion:IOCS is safe and effective in cesarean section, which could save the medical resources and reduces medical expenses, however, it is necessary to strictly master the application indication.

Short term outcomes and respiratory complications after pulmonary endarterectomy: results from a single Chinese center / 中华胸心血管外科杂志

Objective:To investigate the short term outcomes and postoperative respiratory complications of patients with chronic thromboembolic pulmonary hypertension(CTEPH) treated by pulmonary endarterectomy(PEA).Methods:45 consecutive CTEPH patients underwent PEA between December 2017 and January 2020 in our institution were enrolled, including 25 females and 20 males. The mean age of operation was 51.2(25-70) years old. 24(53.5%) patients were in New York Heart Association(NYHA) functional class Ⅲ-Ⅳ. The mean PVR before operation was 923(461-2 711) dyn·s·cm -5. All patients’ data were entered in a prospective database, divieded into patients with respiratory complications group(WRC)and without respiratory complications group(WORC). To assess risk factors for postoperative respiratory complications and its effect on short term outcomes. Results:There was a significant reduction in mPAP(from 37 mmHg to 20 mmHg) and PVR(from 923 dyn·s·cm -5 to 293 dyn·s·cm -5) in the entire group. The in-hospital mortality rate was 4.4%(2 cases), died due to postoperative cardiogenic circulatory failure, even with VA-ECMO treatment and mediastinal infection, respectively. Postoperative respiratory complications occurred in 32 patients(71.1%). The most common complications were reperfusion pulmonary edema 44.4%(20 cases) and residual pulmonary hypertension 11.1%(5 cases). The WRC group showed a tendency to have longer periods of mechanical ventilation, longer ICU stays and more ICU costs. Independent predictors of postoperative respiratory complications were time from symptom onset to PEA>36 months( OR=12.2, 95% CI: 2.1-70.7, P=0.005)and six-minute walking distance<300 m( OR=12.6, 95% CI: 1.1-138.0, P=0.0038). Conclusion:Pulmonary endarterectomy is an effective and safe treatment for CTEPH. Postoperative respiratory complications were mainly determined by symptom onset time and pre-operative status. Patients with CTEPH should consider PEA surgery early.

Effects of sedative drugs on diaphragm activity and the timing of extubation in elderly patients after elective surgery / 中华老年医学杂志

Objective:To investigate the effects of sedatives on the activity of the diaphragm assessed by ultrasound and the timing of extubation in elderly patients after elective surgery.Methods:All 60 eligible elderly patients were randomly divided into three groups: the propofol group, the midazolam group and the control group(n=20, each group). Remifentanil was used in the three groups to keep the Critical Care Pain Observation Tool(CPOT)score less than 3.Patients in the propofol and midazolam groups were given propofol and midazolam sedation respectively, and the Richmond Agitation Sedation Scale(RASS)score was maintained at -2.Diaphragmatic activity was measured, the time from the end of the operation to extubation was recorded, and delirium was evaluated, and the above results were compared with those of the control group, which did not receive sedatives.Results:The activity of the diaphragm was lower in the propofol and midazolam groups than in the control group[(1.10±0.12)cm, (1.17±0.30)cm vs.(1.63±0.25)cm, F=30.170, P=0.000], and there was no significant difference between the propofol group and the midazolam group( t=25.340, P=0.615). There was no significant difference in duration of extubation among the propofol, midazolam and control groups[(1.41±2.08)d, (1.25±1.53)d vs.(1.19±1.40)d, F=0.089, P=0.915]. The incidence of delirium was higher in the midazolam group than in the propofol and control groups[55.0%(11/20), 20.0%(4/20) vs.15.0%(3/20), χ2=5.230, P=0.022, χ2=7.030, P=0.008)], but the difference between the propofol group and control group was not statistically significant( χ2=0.170, P=0.677). Conclusions:The application of sedatives after elective surgery has an effect on the activity of the diaphragm in elderly patients, and the effects of propofol and midazolam are similar.However, propofol and midazolam have no influence on the duration of extubation in elderly patients after elective surgery.Compared with propofol, midazolam increases the incidence of delirium in elderly patients after elective surgery.

Progress in nutrition treatment for severe pneumonia / 中国医师杂志

Severe pneumonia is a common disease in intensive care unit (ICU), which is characterized by acute onset, poor prognosis, and can cause multiple systems dysfunction. For critical ill patients, in a state of stress, catabolism is increased, and nutritional risk is extremely high. Proper nutrition treatment can reduce the decomposition of own tissues in the stress period and supplement the protein and energy needed by the body′s metabolism. Therefore, the nutritional treatment of severe pneumonia patients is particularly important. This paper mainly reviews the nutritional literatures of severe pneumonia and critical ill patients in recent years, in order to provide more appropriate nutritional treatment for severe pneumonia patients.

Noninvasive prenatal screen of trisomy-21 using maternal plasma fetal free RNA allelic ratio / 中华妇产科杂志

Objective Through the detections of the heterozygote frequencies tests of fetal specific genes PLAC4 and COL6A2 mRNA alleles in plasma of pregnant women, to explore its possibility of application in the noninvasive prenatal screenings of trisomy-21. Methods A toltal of 500 cases (males and females 250 cases respectively)of Han ethnic groups with Henan Provice of China who were subject to the physical checkup clinic of the Third Affiliated Hospital,Zhengzhou University from June to December, 2013 were selected as the healthy physical checkup group, and such techniques as DNA sequencing and PCR-restriction fragment length polymorphism (RFLP) were adopted to the determinations of the heterozygote frequencies of the single nucleotide polymorphism(SNP)of the PLAC4 and COL6A2 genes in the maternal peripheral blood in the healthy physical checkup group, and the differential comparisons of the determination results of the SNP heterozygote frequencies and the corresponding heterozygote frequencies in the National Center for Biotechnology Information (NCBI) database;30 cases of healthy pregnant women who spontaneously underwent pregnancy checkups at the maternity clinic were randomly selected as the healthy pregnancy group, and real-time fluorescence quantitative reverse transcription-PCR technique was adopted for determining the expression levels of PLAC4 and COL6A2 mRNA in the peripheral blood of pregnant women of 8 weeks, 10 weeks, 12 weeks, 14 weeks and 16 weeks;40 cases of the same phase were selected for acting as the specimens for the karyotype analyses of the amniotic fluid cells, among which 20 cases were trisomy-21, and the 20 cases of the negative control group, and reverse transcription-multiplex ligation dependent probe amplification (RT-MLPA) technique was adopted for screening the fetal trisomy-21. Results (1) The allele heterozygote frequencies of the SNP of the healthy physical checkup group:determinations of the genotypes and hybrid rates of the 10 SNP sites of the PLAC4 and COL6A2 genes indicated that those with higher heterozygote frequencies were respectively rs7717, rs559, rs1044598, rs59066201 and rs1042917, with population coverage of 98%. Among them, the allele hybrid rates of rs59066201 were never seen in the NCBI database;in the respective comparisons of the allele hybrid rates of rs8130833, rs9977003 and rs7844 with the hybrid rates of the NCBI database, the variations had statistical significance (P0.05);in the mutual comparisons among the expression levels of the various pregnancy weeks, the variations had statistical significance (P<0.05). The expression levels of COL6A2 mRNA in 8 weeks, 10 weeks, 12 weeks, 14 weeks and 16 weeks were respectively 8.95 ± 1.28, 11.19 ± 1.36,15.00 ± 1.58,16.87 ± 1.72 and 18.96 ± 2.79, with their expression levels rising along with the increase of the pregnancy weeks, and in the mutual comparisons between the expression levels of the various pregnancy weeks, the variations all had statistical significance (P<0.05). (3) Prenatal screenings of trisomy-21 in the validation group of the trisome:a total of 5 sites of rs7717, rs559, rs1044598, rs59066201 and rs1042917 were selected from the allele heterozygote frequencies of SNP sites were selected from the subjects of the healthy physical checkup group, and 10 cases of trisomy-21 specimens and 10 cases of negative CTR specimens were accurately determined, with the sensitivity reached 80%(17/20), and the specificity reached 90%(18/20). One case of the trisomy-21 and two negative cases were both homozygotes, and among the trisomy-21 specimens of two cases, only one SNP was a heterozygote, and it was impossible to conduct screenings on these 5 cases, with the screening accuracy reaching 100%(35/35). Conclusions Fetal specific genes PLAC4 and COL6A2 mRNA are expressed in the peripheral blood of pregnant women in different gestational age;its expression level increases with the increase of gestational age. Among them, five SNP including rs7717, rs559, rs1044598, rs59066201 and rs1042917 show highest heterogeneity rate, which is different from the corresponding heterogeneity rate in NCBI database. RT-MLPA technology is a rapid, effective, noninvasive and low cost method of prenatal screening 21 trisomy.